METABOLIC ACTION OF THE CARDIAC GLYCOSIDES. II. EFFECT OF OUABAIN AND DIGOXIN ON THE ENERGY-RICH PHOSPHATE CONTENT OF THE HEART

¹ Carlsberg Laboratorium, Chemical Department, Copenhagen, Valby, Denmark

1. Poisoning the hearts of dogs and of dog heart-lung preparations with ouabain or digoxin to the extent of producing ventricular tachycardia or ventricular fibrillation caused a severe depletion of the phosphocreatine stores of the tissue. The ATP levels were slightly lowered or remained unchanged.

2. No changes in the phosphocreatine and ATP content of the heart occurred as long as the action of the cardiac glycosides was chiefly positive inotropic or restricted to producing signs of toxicity short of ventricular tachycardia.

3. Acceleration of the heart by means of electrical stimulation had no effect on the content of the energy-rich phosphates. Slowing the heart by means of cooling the sinus node led to an increase in the phosphocreatine content of the heart muscle.

4. Aerobic phosphorylation of creatine by dog heart muscle tissue was unaffected even by relatively high concentrations of ouabain.

5. These results have been discussed in the light of present knowledge of the chemistry of muscular contraction and of the influence of the cardiac glycosides on the function and metabolism of the heart and have been interpreted as constituting support for the hypothesis that the cardiac glycosides facilitate the utilization of adenosine triphosphate by the contractile system of the myocardium.